the tolerability，safety，pk/pd study of rhtpo in the patients with liver function impairment

Conditions: Liver Cirrhosis

Summary: the purpose of this study is to evaluate the tolerability, safety, pharmacokinetics and pharmacodynamics of recombinant human thrombopoietin in the patients with different degree of liver function impairment according child- pugh class.

this is a randomized, double-blind, placebo controlled, dose-escalation phase ia study to evaluate the tolerability, safety, pharmacokinetics and pharmacodynamics of recombinant human thrombopoietin. according child- pugh class of liver function impairment and different dose of recombinant human thrombopoietin, nine arms be designed in this study. each subject in arm a will be only administered recombinant human thrombopoietin. each subject in arm b and c will be randomly assigned to accept either recombinant human thrombopoietin or placebo in 5:1 ratio.

Eligibility criteria:
inclusion criteria: * 1. patients with cirrhosis caused by chronic liver disease who have been diagnosed by biopsy/imaging (child-pugh class a, b, and c). * 2. life expectancy≥3 months. * 3. platelet count≤80×109/ l. * 4. fertile female subjects with a negative pregnancy test during the screening period and who agree to take effective contraceptive methods throughout the study period will be eligible for this study. * 5. voluntary written informed consent. exclusion criteria: * 1 subjects allergic to any component of investigational drug. * 2 subjects with cirrhosis caused by drug-induced liver injury. * 3 subjects with history of splenectomy or liver transplantation. * 4 liver cirrhosis with serious complications, including: hepatic encephalopathy, intractable ascites, upper gastrointestinal bleeding, etc. * 5 subjects with liver failure. * 6 tthe presence of portal vein thrombosis or tumor thrombus was indicated by doppler ultrasound or ct or mri and other imaging examinations within 3 months prior to the beginning of screening. * 7 subjects with history of arterial or venous thromboembolism, or with thromboembolic disease, or with high risk factors for thrombosis, or with a hereditary tendency to thrombosis, including antithrombin iii deficiency, etc. * 8 subjects with history of any disease other than chronic liver disease and cirrhosis that may result in decreased platelet count and/or abnormal platelet function, including aplastic anemia, myelodysplastic syndrome (mds), bone marrow fibrosis, etc.; * 9 subjects with diseases with higher bleeding risk, such as coagulation factor deficiency or vascular pseudohemophilia factor deficiency. * 10 subjects with severe infections that are not effectively controlled. * 11 past or present history with any serious disease except liver disease, including: angina, severe arrhythmia, myocardial infarction, heart failure, cerebral hemorrhage, cerebral infarction, intracranial infection, renal insufficiency( creatinine clearance rate ≤50 ml/min )，as well as any other diseases that have been judged by investigator to be unsuitable for this study. * 12 subjects who had undergone trans jugular intrahepatic portal shunt (tips); * 13 subjects with anti-hiv positive antibodies or anti- tpha positive antibodies. * 14 subjects who received any therapy with increased platelet count within the 3 weeks or platelet transfusion within 2 weeks before randomization. * 15 no more than 30 days or 5 half-lives after investigational drug treatment for other studies (whichever is longer). * 16 subjects with history of primary liver cancer, or an other malignant tumor. * 17 patients with who≥grade 2 of existing active bleeding, or with history of active bleeding within 2 weeks before randomization. * 18 pregnant or breast-feeding women. * 19 women who have a pregnancy plan within 3 months. * 20 subjects with history of drug abuse and alcoholism within 6 months prior to enrollment. * 21 subjects who do not have the sufficient ability of understanding，communication and cooperation leading to failure to ensure compliance with protocol will be excluded.